Potential predictive value of CD8A and PGF protein expression in gastric cancer patients treated with neoadjuvant immunotherapy

Background Immunoneoadjuvant therapy has garnered considerable attention owing to significant strides in cancer treatment. We aimed to explore the molecular mechanisms underpinning immunoneoadjuvant therapy through a comprehensive multiomics analysis using samples from a registered clinical trial cohort. Methods Preoperative samples were collected from 16 patients, and postoperative samples were obtained from 12 among them. RNA-seq and Olink proteomics were employed to identify key genes before and after neoadjuvant treatment. The weighted coexpression network was constructed using Weighted gene co-expression network analysis (WGCNA). Furthermore, the proportion of infiltrated immune cells was calculated using xCell based on normalized expression data derived from RNA-seq. Results Patients were stratified into T1 (good efficacy) and T2 (poor efficacy) groups based on Tumor Regression Grade (TRG) to neoadjuvant immunotherapy. Compared to the T2 group (TRG2 and TRG3), the T1 group (TRG0 and TRG1) showed significant differences in pathways related to inflammatory response and myeloid leukocyte activation. Furthermore, the T1 group exhibited elevated levels of CD8 + T cells and B cells. The top two factors with the highest area under the Receiver Operating Characteristic (ROC) curve were CD8a molecule (CD8A) (1.000) and C-C motif chemokine ligand 20 (CCL20) (0.967). Additionally, the expression of Placenta Growth Factor (PGF) and TNF receptor superfamily member 21 (TNFRSF21) proteins significantly increased compared to the T2 group. High expression of CD8A and PGF were associated with favorable and poor prognosis in gastric cancer patients, respectively. Immunoinfiltration analysis revealed a positive correlation between CD8A and Dendritic Cell (DC) levels, while a negative correlation was observed with Myeloid-derived suppressor cell (MDSC) levels. Conclusions Through multiomics analysis, we discovered that CD8A is linked to enhanced treatment response and tumor regression. Conversely, PGF exhibited contrasting effects, hinting at a potential adverse influence on treatment outcomes.